Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial

Background. To comprehensively assess the effects of metformin added to insulin on metabolic control, insulin sensitivity, and cardiovascular autonomic function in adolescents with type 1 diabetes. Materials and Methods. This was an exploratory, crossover, randomized trial conducted in adolescents with type 1 diabetes aged 12-18 years old. Participants were randomly received metformin (≤1000 mg/d) added to insulin for 24 weeks followed by insulin monotherapy for a subsequent 24 weeks or vice versa. Blood pressure, body mass index, insulin dose, estimated insulin sensitivity, glycated hemoglobin A1c (HbA1c), and lipid profiles were measured, with a 72-hour continuous glucose monitoring and 24-hour Holter monitoring performed at baseline, 24, and 50 weeks for the assessments of glucose variability and heart rate variability. Results. Seventeen patients with mean ± SD age 14.4 ± 2.3 years , body mass index 18.17 ± 1.81 kg / m 2 , median (IQR) diabetes duration 4.50 (3.58, 6.92) years, and HbA1c 9.0% (8.5%, 9.4%) were enrolled. The between-group difference in HbA1c of 0.28% (95% CI -0.39 to 0.95%) was not significant ( P = 0.40 ). Changes in body mass index, insulin dose, blood pressure, lipid profiles, and estimated insulin sensitivity were similar for metformin add-on vs. insulin monotherapy. Glucose variability also did not differ. Compared with insulin monotherapy, metformin add-on significantly increased multiple heart rate variability parameters. Conclusions. Metformin added to insulin did not improve metabolic control or glucose variability in lean/normal-weight adolescents with type 1 diabetes. However, metformin added to insulin significantly increased heart rate variability, suggesting that metformin might improve cardiovascular autonomic function in this population.

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Three-Variate Longitudinal Patterns of Metabolic Control, Body Mass Index, and Insulin Dose during Puberty in a Type 1 Diabetes Cohort: A Group-Based Multitrajectory Analysis

The Journal of Pediatrics ◽

10.1016/j.jpeds.2019.11.012 ◽

2020 ◽

Vol 218 ◽

pp. 64-71.e3

Author(s):

Anke Schwandt ◽

Oliver Kuss ◽

Desiree Dunstheimer ◽

Beate Karges ◽

Thomas Kapellen ◽

...

Keyword(s):

Body Mass Index ◽

Type 1 Diabetes ◽

Metabolic Control ◽

Body Mass ◽

Insulin Dose ◽

Longitudinal Patterns ◽

Control Body

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Serum leptin concentrations in children with type 1 diabetes mellitus: Relationship to body mass index, insulin dose, and glycemic control

Metabolism ◽

10.1053/meta.2002.30502 ◽

2002 ◽

Vol 51 (3) ◽

pp. 292-296 ◽

Cited By ~ 29

Author(s):

Ashraf T. Soliman ◽

Magdi Omar ◽

Hala M. Assem ◽

Ibrahim S. Nasr ◽

Mohamed M. Rizk ◽

...

Keyword(s):

Diabetes Mellitus ◽

Body Mass Index ◽

Type 1 Diabetes ◽

Glycemic Control ◽

Type 1 Diabetes Mellitus ◽

Body Mass ◽

Insulin Dose ◽

Serum Leptin

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Leptin is associated with cardiopulmonary fitness independent of body-mass index and insulin sensitivity in adolescents with type 1 diabetes: a brief report from the EMERALD study

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2017.02.019 ◽

2017 ◽

Vol 31 (5) ◽

pp. 850-853 ◽

Cited By ~ 2

Author(s):

Petter Bjornstad ◽

Melanie Cree-Green ◽

Amy Baumgartner ◽

Gregory Coe ◽

Yesenia Garcia Reyes ◽

...

Keyword(s):

Body Mass Index ◽

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Body Mass ◽

Cardiopulmonary Fitness

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Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes

Acta Endocrinologica ◽

10.1530/eje-07-0090 ◽

2007 ◽

Vol 157 (1) ◽

pp. 31-38 ◽

Cited By ~ 38

Author(s):

J-M González-Clemente ◽

C Vilardell ◽

M Broch ◽

A Megia ◽

A Caixàs ◽

...

Keyword(s):

Insulin Resistance ◽

Heart Rate ◽

Heart Rate Variability ◽

Type 1 Diabetes ◽

Systemic Inflammation ◽

Insulin Dose ◽

Plasma Concentrations ◽

Glucose Disposal ◽

Low Grade

Objective: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. Design: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. Methods: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor α receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. Results: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (r=−0.244, P=0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; r=−0.231, P=0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. Conclusions: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.

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Predictors of abnormal cardiovascular autonomic function measured by frequence domain analysis of heart rate variability and conventional tests in patients with type 1 diabetes

Diabetes Care ◽

10.2337/diacare.23.11.1686 ◽

2000 ◽

Vol 23 (11) ◽

pp. 1686-1693 ◽

Cited By ~ 29

Author(s):

S. Makimattila ◽

A. Schlenzka ◽

M. Mantysaari ◽

R. Bergholm ◽

P. Summanen ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Type 1 Diabetes ◽

Autonomic Function ◽

Domain Analysis ◽

Cardiovascular Autonomic Function ◽

Conventional Tests

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Gastric Emptying Is More Rapid in Adolescents With Type 1 Diabetes and Impacts on Postprandial Glycemia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1055 ◽

2015 ◽

Vol 100 (6) ◽

pp. 2248-2253 ◽

Cited By ~ 21

Author(s):

Shiree J. Perano ◽

Chris K. Rayner ◽

Stamatiki Kritas ◽

Michael Horowitz ◽

Kim Donaghue ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Type 1 Diabetes ◽

Blood Glucose ◽

Gastric Emptying ◽

Autonomic Function ◽

Interquartile Range ◽

Postprandial Glycemia ◽

Emptying Time

Context: Gastric emptying is a critical determinant of postprandial glycemic control in health and type 1 diabetes. There are few studies that assess the relationship between gastric emptying and postprandial glycaemia in adolescents with type 1 diabetes. Objective: The objectives of the study were to quantify gastric emptying in adolescents with type 1 diabetes and examine its relationship to postprandial glycaemia and autonomic function. Design: This was a case-control study. Gastric half-emptying time of a solid meal was measured by a 13C-octanoate breath test. Cardio-autonomic function was measured by heart rate variability. Chronic and postprandial gastrointestinal symptoms were evaluated by questionnaire and visual analog scales. Blood glucose concentrations were monitored frequently during the study. Setting: The study was conducted at a tertiary pediatric hospital in South Australia. Participants: Thirty adolescents (aged 15 ± 2.5 y) with type 1 diabetes and age- and sex-matched controls (gastric emptying, n = 20; heart rate variability, n = 135) participated in the study. Main Outcome: Gastric half-emptying time was the main outcome in the study. Results: Gastric emptying was more rapid in subjects with type 1 diabetes than controls [median half emptying time 78 (interquartile range 61–99) vs 109 (interquartile range 71–124) min, P = .02]. The postprandial rise in blood glucose at 60 minutes was strongly related to gastric half-emptying time (R = −0.65, P = .0001). Gastric emptying was slower in subjects with fasting hyperglycemia but was not related to heart rate variability. Nausea, bloating, and anxiety were related to fasting glycemia (P = .03). Conclusion: Rapid gastric emptying is a major determinant of postprandial glycemia in adolescents with type 1 diabetes. This observation has significant implications for therapy.

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